# Tissue destruction and healing in Celiac Disease

> **NIH NIH RC2** · UNIVERSITY OF CHICAGO · 2023 · $2,394,001

## Abstract

PROJECT SUMMARY
Celiac disease (CeD) is a complex T cell-mediated enteropathy induced by dietary gluten in HLA-DQ2+ and/or
HLA-DQ8+ individuals, which currently affects 1% of the global population. A gluten-free diet (GFD) is, to this
date, the treatment of choice for CeD. However, 50% of CeD patients are unable to effectively adhere to a diet
that sustainably excludes gluten, with many patients suffering from inadvertent gluten exposure. Moreover, over
30% of CeD patients have persistent high symptom burdens, resulting from continued mucosal damage, despite
adhering to a GFD. Persistent mucosal damage on a GFD is associated with several severe complications,
including malignancies, especially lymphomas and bone diseases. In addition, patients with active CeD display
a wide range of clinical presentations, including metabolic defects (vitamins, iron, and cholesterol) that are not
correlated to the degree of tissue damage. Although much progress has been made in understanding CeD,
major gaps remain, notably regarding the biological mechanisms involved in different clinical presentations and
the inconsistent healing process. For instance, it is poorly understood why, independently from the degree of
villous atrophy, certain patients display nutrient and lipid deficiencies, whereas others have normal levels of
vitamins, cholesterol, and iron. Furthermore, while there is evidence for a role of the microbiome in CeD, we lack
information on small-intestinal mucosal microbiota in human CeD (which is more likely to have metabolic effects
and directly interact with the immune system). Finally, we have little knowledge about interactions between gluten,
intestinal epithelial cells (IECs), immune cells, and the microbiota, and how they are linked to the different CeD
clinical phenotypes. Our RC2 proposal will test the hypothesis that CeD is a heterogeneous disorder, while
attempting to define interactions between IECs, microbiota, immune system, and genetics that underlie
differences in clinical presentation, severity of tissue destruction, and the ability to heal. It will also
address critical gaps in our understanding of CeD pathogenesis and clinical presentations, and develop
tools for non-invasive monitoring of CeD patients. We have assembled a team of internationally recognized
experts in the field of CeD, epithelial cell biology, mucosal immunology, microbiome, and chemistry. The RC2
proposal is anchored around multi-omics studies performed in the context of cross-sectional and interventional
gluten challenge and de-challenge studies, on 445 well-characterized adult and pediatric patients. The proposed
specific aims are: 1) Developing an approach to precision medicine in CeD; 2) Deciphering the mechanisms
associated with tissue destruction and healing in CeD, 3) Developing non-invasive tools for monitoring CeD
patients, and 4) Developing research resources for the scientific and medical community to advance patient care
as well as discovery-based and ...

## Key facts

- **NIH application ID:** 10705152
- **Project number:** 5RC2DK133947-02
- **Recipient organization:** UNIVERSITY OF CHICAGO
- **Principal Investigator:** Luis Bruno Barreiro
- **Activity code:** RC2 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $2,394,001
- **Award type:** 5
- **Project period:** 2022-09-15 → 2027-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10705152

## Citation

> US National Institutes of Health, RePORTER application 10705152, Tissue destruction and healing in Celiac Disease (5RC2DK133947-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10705152. Licensed CC0.

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